Variant 2-111123784-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_138621.5(BCL2L11):c.39C>T(p.Asp13=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00411 in 1,448,578 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0042 ( 19 hom. )

Consequence

BCL2L11
NM_138621.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.51

Variant links:

Genes affected

BCL2L11 (HGNC:994): (BCL2 like 11) The protein encoded by this gene belongs to the BCL-2 protein family. BCL-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. The protein encoded by this gene contains a Bcl-2 homology domain 3 (BH3). It has been shown to interact with other members of the BCL-2 protein family and to act as an apoptotic activator. The expression of this gene can be induced by nerve growth factor (NGF), as well as by the forkhead transcription factor FKHR-L1, which suggests a role of this gene in neuronal and lymphocyte apoptosis. Transgenic studies of the mouse counterpart suggested that this gene functions as an essential initiator of apoptosis in thymocyte-negative selection. Several alternatively spliced transcript variants of this gene have been identified. [provided by RefSeq, Jun 2013]

BCL2L11 links:

MIR4435-2HG (HGNC:35163): (MIR4435-2 host gene)

MIR4435-2HG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 2-111123784-C-T is Benign according to our data. Variant chr2-111123784-C-T is described in ClinVar as [Benign]. Clinvar id is 775750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.51 with no splicing effect.

BS2

High AC in GnomAd4 at 520 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2L11	NM_138621.5 linkuse as main transcript	c.39C>T	p.Asp13=	synonymous_variant	2/4	ENST00000393256.8	NP_619527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2L11	ENST00000393256.8 linkuse as main transcript	c.39C>T	p.Asp13=	synonymous_variant	2/4	1	NM_138621.5	ENSP00000376943	P1	O43521-1
MIR4435-2HG	ENST00000645030.2 linkuse as main transcript	n.453-86862G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00342

AC:

520

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000918

Gnomad AMI

AF:

0.0231

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00489

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00345

AC:

534

AN:

154634

Hom.:

AF XY:

0.00366

AC XY:

299

AN XY:

81794

show subpopulations

Gnomad AFR exome

AF:

0.000741

Gnomad AMR exome

AF:

0.00287

Gnomad ASJ exome

AF:

0.0166

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00112

Gnomad FIN exome

AF:

0.00143

Gnomad NFE exome

AF:

0.00482

Gnomad OTH exome

AF:

0.00373

GnomAD4 exome

AF:

0.00419

AC:

5431

AN:

1296342

Hom.:

Cov.:

AF XY:

0.00399

AC XY:

2517

AN XY:

630982

show subpopulations

Gnomad4 AFR exome

AF:

0.000813

Gnomad4 AMR exome

AF:

0.00353

Gnomad4 ASJ exome

AF:

0.0128

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00150

Gnomad4 FIN exome

AF:

0.00173

Gnomad4 NFE exome

AF:

0.00457

Gnomad4 OTH exome

AF:

0.00412

GnomAD4 genome

AF:

0.00342

AC:

520

AN:

152236

Hom.:

Cov.:

AF XY:

0.00316

AC XY:

235

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.000915

Gnomad4 AMR

AF:

0.00301

Gnomad4 ASJ

AF:

0.0156

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00490

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00248

Hom.:

Bravo

AF:

0.00361

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over